Mammalian cells cultured in vitro will be used for studies of low dose rate irradiaton. Some aims have pragmatic usefulness in radiotherapy but the principal thrust is a more basic understanding of the interaction of radiation with biological material. The present study of the Relative Biological Effectiveness (RBE) of Iodine-125 will be extended to include mitotic delay as an endpoint, because of the observation that RBE values are higher for tumor cells which maintain a high growth fraction in plateau phase. The radiobiological properties of Americium-241 at low dose rate will be studied because of its potential use in brachytherapy. Its low energy emission reduces problems of protection, while its 400 year half-life makes it more economic than Iodine-125 for temporary implants. A variety of cells of human origin will be used both normal and malignant, to assess the relative role of potentially lethal and sublethal damage repair in the response to low dose-rate. Our limited studies to date indicate that PLDR is more important and SLDR less important in human than in rodent cells, and also that PLDR occurs in normal as well as malignant cells. Low dose rate irradiation will be used to predict the initial slope of the acute survival curve and where possible correlated with clinical responsiveness in a range of human tumor cell lines. Genetically deficient human cells will be studied, specifically cells from patients suffering from Ataxia Telangectasia, Xeroderma Pigmentosum, Bloom's Syndrome and 5-oxoprolinurea. The role of halogenated pyrimidines as sensitizers with low dose rate irradiation as used in brachytherapy will be studied. The possibility that incorporated IUdR or BUdR may interact strongly with the soft emission from Iodine-125 or Americium-241 will be investigated. The preliminary observation that the mix of different types of chromosome aberrations varies with dose will be investigated. In particular an attempt will be made to assess whether the spectrum of chromosome aberrations is the same for high doses at low dose rate as for low doses in acute exposures. This investigation bears on the validity of the hypothesis that the low dose rate survival curve is an extrapolation of the initial slope of the acute survival curve.